Skip to main content
placeholder image

Microbeam irradiation of the beating rodent heart: an ex vivo study of acute and subacute effects on cardiac function.

Journal Article


Abstract


  • Purpose

    Microbeam radiation therapy (MRT) has shown several advantages compared to conventional broad-beam radiotherapy in small animal models, including a better preservation of normal tissue function and improved drug delivery based on a rapidly increased vascular permeability in the target region. Normal tissue tolerance is the limiting factor in clinical radiotherapy. Knowledge of the normal tissue tolerance of organs at risk is therefore a prerequisite in evaluating any new radiotherapy approach. With an irradiation target in the thoracic cavity, the heart would be the most important organ at risk.

    Methods and materials

    We used the ex vivo beating rodent heart in the Langendorff perfusion system at the synchrotron in order to administer microbeam irradiation (MBI) with a peak dose of 40 or 400 Gy. By continuously recording the electrocardiogram, the left ventricular pressure, and the aortic pressure before, during and after MBI, we were able to assess acute and subacute effects of MBI on electrophysiological and mechanical cardiac function. In addition, we analyzed histological and ultrastructural sequelae caused by MBI.

    Results

    There were no significant changes in heart rate, heart rate variability, systolic increase of left ventricular pressure or aortic pressure. Moreover, the changes of heart rate, left ventricular pressure and aortic pressure by adding 10-5 mol/l norepinephrine to the perfusate, were also not significant between MBI and sham experiments. However, the rate-pressure product as a surrogate marker for maximum workload after MBI was significantly lower compared to sham-irradiated controls. On the structural level, no severe membranous, sarcomeric, mitochondrial or nuclear changes caused by MBI were detected by desmin immunohistochemistry and electron microscopy.

    Conclusion

    With respect to acute and subacute toxicity, an MBI peak dose up to 400 Gy did not result in severe changes in cardiac electrophysiology or mechanics.

UOW Authors


  •   Lerch, Michael (external author)
  •   Davis, Jeremy (external author)

Publication Date


  • 2022

Citation


  • Lange, F., Kirschstein, T., Davis, J., Paino, J., Barnes, M., Klein, M., . . . Schültke, E. (2022). Microbeam irradiation of the beating rodent heart: an ex vivo study of acute and subacute effects on cardiac function.. International journal of radiation oncology, biology, physics, S0360-3016(22)00399-6. doi:10.1016/j.ijrobp.2022.05.001

Web Of Science Accession Number


Start Page


  • S0360-3016(22)00399-6

Abstract


  • Purpose

    Microbeam radiation therapy (MRT) has shown several advantages compared to conventional broad-beam radiotherapy in small animal models, including a better preservation of normal tissue function and improved drug delivery based on a rapidly increased vascular permeability in the target region. Normal tissue tolerance is the limiting factor in clinical radiotherapy. Knowledge of the normal tissue tolerance of organs at risk is therefore a prerequisite in evaluating any new radiotherapy approach. With an irradiation target in the thoracic cavity, the heart would be the most important organ at risk.

    Methods and materials

    We used the ex vivo beating rodent heart in the Langendorff perfusion system at the synchrotron in order to administer microbeam irradiation (MBI) with a peak dose of 40 or 400 Gy. By continuously recording the electrocardiogram, the left ventricular pressure, and the aortic pressure before, during and after MBI, we were able to assess acute and subacute effects of MBI on electrophysiological and mechanical cardiac function. In addition, we analyzed histological and ultrastructural sequelae caused by MBI.

    Results

    There were no significant changes in heart rate, heart rate variability, systolic increase of left ventricular pressure or aortic pressure. Moreover, the changes of heart rate, left ventricular pressure and aortic pressure by adding 10-5 mol/l norepinephrine to the perfusate, were also not significant between MBI and sham experiments. However, the rate-pressure product as a surrogate marker for maximum workload after MBI was significantly lower compared to sham-irradiated controls. On the structural level, no severe membranous, sarcomeric, mitochondrial or nuclear changes caused by MBI were detected by desmin immunohistochemistry and electron microscopy.

    Conclusion

    With respect to acute and subacute toxicity, an MBI peak dose up to 400 Gy did not result in severe changes in cardiac electrophysiology or mechanics.

UOW Authors


  •   Lerch, Michael (external author)
  •   Davis, Jeremy (external author)

Publication Date


  • 2022

Citation


  • Lange, F., Kirschstein, T., Davis, J., Paino, J., Barnes, M., Klein, M., . . . Schültke, E. (2022). Microbeam irradiation of the beating rodent heart: an ex vivo study of acute and subacute effects on cardiac function.. International journal of radiation oncology, biology, physics, S0360-3016(22)00399-6. doi:10.1016/j.ijrobp.2022.05.001

Web Of Science Accession Number


Start Page


  • S0360-3016(22)00399-6